The highest bioterrorism threat pathogens, the Category A agents, have the greatest potential for adverse public health impact and mass casualties if used in ill-intentioned ways. Among the Category A viruses, there are five hemorrhagic fever arenaviruses (Lassa, Junin, Machupo, Guanarito and Sabia viruses). Currently, there are no specific antiviral treatments approved for use against arenavirus hemorrhagic fevers. The overall goal of our arenavirus antiviral program is to advance through FDA approval at least one small molecule antiviral drug for treatment and prevention of viral hemorrhagic fever due to Category A arenaviruses that will be safe, effective and orally administered as a capsule, tablet or liquid for treatment, post-exposure prophylactic and prophylactic applications. The objective of this SBIR Phase II Arenavirus project is to advance the early stage arenavirus-specific antiviral compounds discovered during our SBIR Phase I work into chemical optimization, through animal efficacy, IND-enabling toxicology and other preclinical activities, to clinical development stage candidates for which we will submit IND applications. Human safety and pharmacokinetic studies are beyond the scope of the Phase II work plan. At the end of this 3-year SBIR Phase II Arenavirus program, we anticipate that we will submit at least one IND application for an antiviral drug candidate for the treatment and prevention of Category A arenavirus infections and identify at least one additional arenavirus preclinical candidate. The availability of arenavirus-specific antiviral drugs will address national and global security needs by acting as significant deterrents and defenses against use of the Category A arenaviruses in potential bioterrorist attacks. Antiviral drugs may be readily stockpiled and rapidly deployed in the event of an arenavirus outbreak. Since antiviral drugs are easily administered (oral pill or liquid) and exert their antiviral effect rapidly (within hours of administration), they will serve to effectively treat diseased patients, protect those suspected of being exposed to the pathogen (post-exposure prophylaxis), and assist in the timely containment of the outbreak. [unreadable] [unreadable]